According to the American Cancer Society about 494,000 people died from cancer in the United States in 1988. One of every five deaths from all causes in the United States is from cancer. Although chemotherapy has become one of the principal methods of treating cancer, the rate at which new drugs have become available for use in cancer chemotherapy has declined in recent years as reported by Horowitz et al. "Phase II Testing of Melphalan in Children with Newly Diagnosed Rhabdomyosarcoma: A Model for Anticancer Drug Development", Journal of Clinical Oncology, Vol. 6, No. 2, pp. 308-314 (1988). Accordingly, there is a substantial need for new drugs which are effective in inhibiting the growth of tumors.
To be particularly useful, a new chemotherapeutic agent should have a wide spectrum of activity, a large therapeutic index, and be chemically stable and compatible with other agents. Additionally, it would be beneficial for the new agent to have oral activity so that initial treatment and subsequent maintenance therapy is more convenient and less traumatic to the patient.
It has now been found that certain thiophenesulfonylureas are particularly useful in the treatment of solid tumors. These compounds are relatively nontoxic and provide an excellent therapeutic index.
Some diarylsulfonylureas have been reported as being active antitumor agents e.g., U.S. Pat. No. 4,845,128 of Harper et al. (1989), Grindey et al. American Association of Cancer Research, Vol. 27, pp 277 (1986) and Houghton et al., Cancer Chemother. Pharmacol., (1989) 25, 84-88. There is no suggestion in these references of the thiophenesulfonylureas of the instant application or that these compounds would be useful as antitumor agents.
Certain thiophenesulfonylurea compounds have been reported. Shawali et al., Journal of Drug Research Egypt, Vol. 5, No. 1 pp. 117 (1973) reported N-thiophenesulfonyl-N'-(4-chlorobenzene)urea. Holland, Journal of Organic Chemistry, Vol. 26, pp. 1662 (1961) reported the preparation of several thiophenesulfonylurea compounds including certain N'-(4-fluorobenzene) compounds. McLamore, U.S. Pat. No. 2,979,437 (1961) discloses a number of arylalkenesulfonylureas as having hypoglycemic activity.
None of these references suggest or disclose the antitumor activity of the thiophenesulfonylurea compounds of the instant invention. Additionally, there is no suggestion or disclosure of the claimed compounds of the instant invention.